Laboratory of Organic Chemistry, ETH Zürich, D-CHAB, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
J Am Chem Soc. 2023 Sep 13;145(36):19513-19517. doi: 10.1021/jacs.3c07006. Epub 2023 Aug 29.
Azomethine imines are valuable substrates for chemical synthesis in organic solvents that often require anhydrous conditions. Here, we introduce ,-cyclic-'-acyl azomethine imines (AMIs) to bioorthogonal reactions in an aqueous environment. These AMIs are stable under physiological conditions and react rapidly ( = 0.1-250 M s, depending on pH) and chemoselectively with isonitriles in the presence of biological nucleophiles, including thiols. Live-cell imaging of cell-surface-bound isonitriles underlines the biocompatibility of the AMI-isonitrile ligation, and simultaneous one-pot triple-protein labeling demonstrates its orthogonality to commonly used bioorthogonal reactions, such as the SPAAC and iEDDA ligations.
亚甲胺叶立德是有机溶剂中化学合成的有价值的底物，通常需要无水条件。在这里，我们在水相环境中引入了β-环-α-酰基亚甲胺叶立德（AMIs）用于生物正交反应。这些 AMIs 在生理条件下稳定，并且在存在生物亲核试剂（包括硫醇）的情况下，与异腈快速（ = 0.1-250 M s，取决于 pH）和化学选择性反应。活细胞成像表明细胞膜结合异腈的 AMI-异腈连接具有生物相容性，同时一锅法三重蛋白质标记证明了其与常用的生物正交反应（如 SPAAC 和 iEDDA 连接）的正交性。
